Rubin R H, Lynch P, Pasternack M S, Schoenfeld D, Medearis D N
Medical Service, Massachusetts General Hospital, Boston 02114.
Antimicrob Agents Chemother. 1989 Nov;33(11):1975-9. doi: 10.1128/AAC.33.11.1975.
The efficacy of treatment with ganciclovir (DHPG) and antibody activity-containing ascitic fluid (AF) separately and in combination was studied in normal and immunosuppressed BALB/c mice challenged intraperitoneally with a lethal dose (10(6) PFU) of murine cytomegalovirus (CMV). With combination therapy, lower doses of both DHPG and AF were often as effective as a higher dose of either agent given singly. For instance, the survival rate of murine CMV-challenged immunosuppressed mice was doubled when 4 mg of DHPG per kg and a 1:16 dilution of AF were both administered in contrast to when each was used alone. In both groups of animals, combination therapy was shown to be more effective than either therapy individually, even when initiation of therapy was delayed as long as 48 h. Such an approach holds promise for decreasing the expense associated with antibody use and the dose-related toxicity associated with DHPG use while maintaining or possibly increasing the efficacy of prophylaxis and therapy of serious CMV disease in humans.
在正常和免疫抑制的BALB/c小鼠中,腹腔注射致死剂量(10(6) PFU)的鼠巨细胞病毒(CMV),研究了更昔洛韦(DHPG)和含抗体活性腹水(AF)单独及联合治疗的效果。联合治疗时,较低剂量的DHPG和AF通常与单独使用较高剂量的任何一种药物效果相同。例如,与单独使用时相比,每千克给予4毫克DHPG和1:16稀释的AF联合给药时,感染鼠CMV的免疫抑制小鼠的存活率提高了一倍。在两组动物中,联合治疗均显示比单独使用任何一种治疗更有效,即使治疗开始延迟长达48小时。这种方法有望在维持或可能提高人类严重CMV疾病预防和治疗效果的同时,降低与抗体使用相关的费用以及与DHPG使用相关的剂量相关毒性。